Vilcek Foundation

Michael Halassa

The Vilcek Prize for Creative Promise in Biomedical Science

Michael Halassa, M.D., Ph.D.

Michael Halassa’s interest in cognition might be traced back to Rene Descartes. Renowned for his musings on the nature of subjective experience, the 17th-century French philosopher and mathematician eloquently distilled the dualism of mind and body intrinsic to the human condition—a phenomenon that continues to preoccupy 21st-century neuroscientists and philosophers alike. Following a line of researchers attempting to unlock the mysteries of human perception and cognition, Halassa has shown how the brain attends to cues in the outside world and sustains prolonged thought, findings that earned him wide acclaim early in his career.

Halassa was born in Amman, Jordan, amid the sociopolitical upheaval wrought by the rise of religious fundamentalism across the Middle East in the late 1970s. Hailing from a family of religious minorities in Jordan, Halassa spent a beleaguered childhood beset by discrimination. So he took refuge in science, and his parents, both physicians, nurtured his growing intellectual appetite. “What I had experienced in my personal life seemed so arbitrary, on a psychological level, science was like an antidote,” he says.

Enamored with the consistency of the quantitative sciences in high school, Halassa set his mind on theoretical physics. But his parents urged him to follow in their footsteps, so he enrolled in medical school in Jordan. While there, he came across the writings of neuroscientist Christoph Koch and molecular biologist Francis Crick, who together seized on the long-elusive phenomenon of consciousness, challenging the Cartesian view of mind-body dualism in compelling treatises published beginning in the 1990s.

Enthralled by the writings, which raised empirical questions on how the brain generates the mind, Halassa grew increasingly fascinated with the seemingly ungraspable nature of reality. Before long, he was convinced that a career in science would lead to personal fulfillment. So when he secured an internship in the lab of an acquaintance at Johns Hopkins University, the moment marked an inflection point. “I was in complete disbelief when I found out that I could go the US for the internship,” recalls Halassa. Eventually, he joined the lab of neuroscientist Solomon Snyder, with whom he developed a taste for experimental biology during a brief stint.

Upon returning to Jordan, Halassa resolved to pursue a research career in neuroscience. Years later, he earned a PhD from the University of Pennsylvania, where his talent was shaped, and performed postdoctoral studies at Massachusetts Institute of Technology, where his current interests were crystallized. Today, as assistant professor at New York University, Halassa’s work is focused on how the brain sifts signals from noise and builds mental representations of the world.

Using deft experimental paradigms to study selective attention, Halassa has brought clarity to a phenomenon that had long puzzled neuroscientists. Housed in a brain region called the thalamus, a group of brain cells called the thalamic reticular nucleus, or TRN, had been suspected to control the brain’s ability to pay selective attention to cues from the outside world. However, the precise role of the cells, which are thought to serve as a switchboard for routing signals through the brain’s cortex, had remained unestablished, partly due to a dearth of methods to probe how lab animals pay attention.

Combining genetics, electrophysiology, and behavioral experiments in freely moving mice, Halassa found that different TRN neurons are active when animals are asleep and awake. TRN neurons that control the flow of sensory signals to the brain are active during sleep, whereas those that control the flow of memory-related signals are active in awake animals. The findings uncovered a mechanism that enables the brain to switch from relaying input from the outside world to inwardly focused processes like thought and memory consolidation. Before long, Halassa went on to demonstrate the central role of TRN neurons in regulating selective attention. “Aside from the conceptual contribution, we essentially made mice cognitively accessible—and this helped overcome a major bottleneck in using mice as cognitive models in neuroscience,” says Halassa, modestly treating a singular achievement as a methodological tangent.

Applying those fundamental insights to human disease, Halassa teamed up with MIT neuroscientist Guoping Feng to unravel how TRN neurons go awry in some patients with a form of autism. Together, they found that the human gene PTCHD1, which is missing in around 1% of patients with autism, plays a crucial role in suppressing noise and allowing the brain to perceive signals unimpeded. The findings suggest that therapeutic interventions aimed at restoring TRN activity might make up for related deficits in patients.

More recently, Halassa has found that the part of the brain’s thalamus that is not involved in processing sensory signals can function as a signal amplifier for the brain’s cortex, providing a tantalizing glimpse of undisclosed findings of fundamental significance to neuroscientists. “This finding shows that the thalamus is much more than a relay station, contributing to the basic brain architecture that supports stable thoughts and representations,” says Halassa.

Coming to the United States was a boon to his personal life and career, says Halassa. “I never felt like an outsider in the US. And I think the US is a real meritocracy; you are rewarded here for how well you think and how hard you work. It is a privilege to be in the country,” he adds.

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